As is known, microfluidic devices are being used in an increasing number of applications. However, further expansion of the uses for such microfluidic devices has been limited due to the difficulty and expense of utilization and fabrication. It can be appreciated that an efficient and simple method for producing pressure-based flow within such microfluidic devices is mandatory for making microfluidic devices a ubiquitous commodity.
Several non-traditional pumping methods have been developed for pumping fluid through a channel of a microfluidic device, including some which have displayed promising results. However, the one drawback to almost all pumping methods is the requirement for expensive or complicated external equipment, be it the actual pumping mechanism (e.g., syringe pumps), or the energy to drive the pumping mechanism (e.g., power amplifiers). The ideal device for pumping fluid through a channel of a microfluidic device would be semi-autonomous and would be incorporated totally at the microscale.
The most popular method of moving a fluid through a channel of a microfluidic device is known as electrokinetic flow. Electrokinetic flow is accomplished by conducting electricity through the channel of the microfluidic device in which pumping is desired. While functional in certain applications, electrokinetic flow is not a viable option for moving biological samples through a channel of a microfluidic device. The reason is twofold: first, the electricity in the channels alters the biological molecules, rendering the molecules either dead or useless; and second, the biological molecules tend to coat the channels of the microfluidic device rendering the pumping method useless. Heretofore, the only reliable way to perform biological functions within a microfluidic device is by using pressure-driven flow. Therefore, it is highly desirable to provide a more elegant and efficient method of pumping fluid through a channel of a microfluidic device.
In addition, as biological experiments become more complex, an unavoidable fact necessitated by the now apparent complexity of genome-decoded organisms, is that more complex tools will be required. Presently, in order to simultaneously conduct multiple biological experiments, plates having a large number (e.g. either 96 or 384) of wells are often used. The wells in these plates are nothing more than holes that hold liquid. While functional for their intended purpose, it can be appreciated that these multi-well plates may be used in conjunction with or may even be replaced by microfluidic devices.
To take advantage of existing hardware, “sipper” chips have been developed. Sipper chips are microfluidic devices that are held above a traditional 96 or 384 well plate and sip sample fluid from each well through a capillary tube. While compatible with existing hardware, sipper chips add to the overall complexity, and hence, to the cost of production of the microfluidic devices. Therefore, it would be highly desirable to provide a simple, less expensive alternative to devices and methods heretofore available for pumping fluid through a channel of a microfluidic device.
Therefore, it is a primary object and feature of the present invention to provide a method of pumping fluid through a channel of a microfluidic device which is simple and inexpensive.
It is a further object and feature of the present invention to provide a method of pumping fluid through a channel of a microfluidic device which is semi-autonomous and requires only minimal additional hardware.
It is a still further object and feature of the present invention to provide a method of pumping fluid through a channel of a microfluidic device which is compatible with preexisting robotic high throughput equipment.
In accordance with the present invention, a method of pumping sample fluid through a channel of a microfluidic device is provided. The method includes the step of providing the channel with an input and an output. The channel is filled with a channel fluid. A first pumping drop of the sample fluid is deposited at the input of the channel such that the first pumping drop flows into the channel through the input.
A second pumping drop of the sample fluid may be deposited at the input of the channel after the first pumping drop flows into the channel. The input of the channel has a predetermined radius and the first pumping drop has a radius generally equal to the predetermined radius of the input of the channel. The first pumping drop has an effective radius of curvature and the fluid at the output has an effective radius of curvature. The effective radius of curvature of the fluid output is greater than the effective radius of curvature of the first pumping drop.
The first pumping drop has a user selected volume and projects a height above the microfluidic device when deposited at the input of the channel. The radius of the first pumping drop is calculated according to the expression:
  R  =            [                                    3            ⁢            V                    π                +                  h          3                    ]        ⁢          1              3        ⁢                                  ⁢                  h          2                    wherein: R is the radius of the first pumping drop; V is the user selected volume of the first pumping drop; and h is the height of the first pumping drop above the microfluidic device.
The method may include the additional step of sequentially depositing a plurality of pumping drops at the input of the channel after the first pumping drop flows into the channel. Each of the plurality of pumping drops is sequentially deposited at the input of the channel as the previously deposited pumping drop flows into the channel. The first pumping drop has a volume and the plurality of pumping drops have volumes generally equal to the volume of the first pumping drop. It is contemplated for the channel fluid to be the sample fluid.
The method may also include the additional step of varying the flow rate of first pumping drop through the channel. The channel has a cross-sectional area and the step of varying the flow rate of first pumping drop through the channel includes the step of reducing the cross-sectional area of at least a portion of the channel.
In accordance with a still further aspect of the present invention, a method of pumping fluid is provided. The method includes the step of providing a microfluidic device having a channel therethough. The channel includes a first input port and a first output port. The channel is filled with fluid and a pressure gradient is generated between the fluid at the input port and the fluid at the output port such that the fluid flows through the channel towards the output port.
The step of generating the pressure gradient includes the step of sequentially depositing pumping drops of fluid at the input port of the channel. Each of the pumping drops has a radius generally equally to the predetermined radius of the input port of the channel. Each of the pumping drops has an effective radius of curvature and the fluid at the first output port has an effective radius of curvature. The effective radius of curvature of the fluid at the output port is greater than the effective radius of curvature of each pumping drop.
The channel has a resistance and each of the pumping drops has a radius and a surface free energy. The fluid at the first output port has a height and a density such that the fluid flows through the channel at a rate according to the expression:
            ⅆ      V              ⅆ      t        =            1      Z        ⁢          (                        ρ          ⁢                                          ⁢          gh                -                              2            ⁢            γ                    R                    )      wherein: dV/dt is the rate of fluid flowing through the channel; Z is the resistance of the channel; ρ is the density of the fluid at the first output port; g is gravity; h is the height of the fluid at the output port; γ is the surface free energy of the pumping drops; and R is the radius of the pumping drops.
In accordance with a still further aspect of the present invention, a method of pumping fluid through a channel of a microfluidic device is provided. The channel has a first input port and an output port. The channel is filled with fluid and pumping drops of fluid are sequentially deposited at the first input port of the channel to generate a pressure gradient between fluid at the input port and fluid at the output port. As a result, the fluid in the channel flows toward the output port.
Each of the pumping drops has an effective radius of curvature and the fluid at the first output port has an effective radius of curvature. The effective radius of curvature of the fluid at the output port is greater than the effective radius of curvature of each pumping drop. In addition, each of the pumping drops has a radius generally equally to the predetermined radius of the input port of the channel.
The method may also include the additional step of varying the flow rate of first pumping drop through the channel. The channel has a cross-sectional area and the step of varying the flow rate of first pumping drop through the channel includes the step of reducing the cross-sectional area of at least a portion of the channel.